Lack of consistent, clear, and adequate source documentation is one of the most typical inspection results in investigator site inspections. This is also the most discovered flaw during sponsor audits. To guarantee that the study results are established on the foundation of trustworthy and legitimate data, investigator sites must be reminded of the need for good documentation practices.
The origins of excellent documentation standards can be found in the (International Conference of Harmonizaton – Good Clinical Practice) ICH-GCP, which defines source data and source documents.
ICH E6 1.51 source data
This includes all original documents and authenticated copies of original records of clinical results, observations, or other activities in a clinical trial that are required for the trial’s restoration and assessment. The documents containing source data are referred to as sources.
ICH E6 1.52 source documents
This includes original documents, data, and records such as hospital records, clinical and office charts. The ALCOA-C acronym (attributable, legible, contemporaneous, original, accurate and complete) was coined by the US Food and Drug Administration to describe key characteristics of acceptable documentation. The World Health Organization has also adopted these. These requirements have changed over time. More ‘letters’ have been added by the EMA to indicate features of good source documentation, particularly for computerized systems.
Common Findings Associated with Source Documentation
Following are the common findings associated with source documentation:
- It was not possible to validate the eligibility criteria.
- Because there were multiple entries for the same data point, it was impossible to tell which one was the correct source record.
- Inconsistencies in records were used to corroborate the study’s primary effectiveness outcome.
- Abnormal lab values were not indicated on lab reports nor any contradicting material gathered in source documentation have been shown clinical importance.
- Missing pieces of information from subject interview scales, a slew of unexplained revisions months after the initial entries, and contradictory data; erroneous subject identification, inaccurate date were identified.
- Factually inaccurate paperwork regarding drug disposition—dates, amount, and subject use were found.
How Can Documentation Be Improved?
Documentation can be improved by the following ways:
- Give PI the responsibility to assign tasks to the trained staff.
- Commitment and continuous presence must be acknowledged by the Principal Investigator (PI) throughout the study.
- Sites conducting the study must prepare SOPs which ought to be shared with the Contract Research Organization (CRO) or study sponsor.
- All technical aspects must be clear of confusions and errors prior to starting work on any study.
- The sponsor and/or the CRO ensure PI’s commitment to the study.
The ALCOA-C and other properties indicated by regulatory agencies and GCP should be demonstrated in source documents. During regular audits, the most frequently stated findings are those linked to source documentation. The PI’s dedication to the trial and participation in it makes a tremendous difference. Efforts to educate sites, understand their practices from the pre-study visit onwards, and to monitor and train them on a regular basis will all aid in increasing and sustaining the quality of site source documentation procedures.
“ALCOA”: Elements of good documentation. (n.d.). Retrieved October 24, 2021, from https://blink.ucsd.edu/research/policies-compliance-ethics/compliance/ALCOA-Standards-210304.pdf.
Bargaje, C. (2011, April). Good documentation practice in clinical research. Perspectives in clinical research. Retrieved October 24, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121265/.
Commissioner, O. of the. (n.d.). List – ich guidance documents. U.S. Food and Drug Administration. Retrieved October 24, 2021, from https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/ich-guidance-documents.
GLP documentation. (2007). Good Laboratory Practice Regulations, 241–258. https://doi.org/10.3109/9780849375842-11